Thank you very much, Bruce, and thank you for everybody for, for logging in. . I'm sorry, as it's turned out that I'm clashing with the BBC's big night in.
Maybe you can go back and watch, on on your TiVo box or something and please remember to, donate some money. It's a very worthwhile cause. Tonight, what I'm going to do is go through, antimicrobial stewardship.
And I know right now this doesn't seem, a, a big problem, but, it is, it will stay with us, . And it is something that, if we, allow, antibiotic resistance to continue and we lose these drugs, it's going to have a massive effect on what we regard as modern healthcare, both in the medical field, and, and the veterinary field. And this is the problem that we have.
So the, the bulk of, antibiotic classes were actually discovered, in the years immediately following the Second World War. And since about the 1970s, we've had no genuine, new classes of drugs that have been licenced for animals. There are, there are some here, but they're all much more specialist drugs, and, and the, the licence is, is only for, only for humans.
Now this means that, you know, every time a new drug comes along. And two examples here would be erfovisin, which is a 3rd generation cephalosporin and Pradafloxacin, which, which is a fluoroquinolone. These are not genuinely new antibiotics.
They are modifications of an existing class of antibiotic, and this is known as the antimicrobial discovery gap. And Alexander Fleming here, when he was given his Nobel Prize for the discovery of penicillin, and he, he got his prize in the mid 1950s as part of his speech, he recognised that this problem was going to arise. And I'll try to get the quote right, but he remarked that the person who misuses antibiotics will become morally culpable.
For the death of the person whose infection cannot now be treated. And the single biggest driver behind the development and spread of antimicrobial resistance is the use of antibiotics, particularly systemic drugs. This is a slide that I've taken from a couple of Vanessa Schmidt's papers.
This is when she was doing her PhD with me at the University of Liverpool. And this is 3 years hard graft really, unfortunately compressed into one slide. But what she did.
Was looked at dogs that were being treated with sys with the systemic antibiotics. This was cephalexin, amoxiclav, cefovain, clindamycin, flu fluoroquinolone. And she took a whole series of samples from these dogs looking at their mucosal bacterial populations, their gut bacterial populations, and looked for bacteria and resistance markers before treatment, immediately after treatment, and then she followed them through for about 3 months.
And what she found is really with, with, without exception. At the end of treatment, there was a significant increase in the level of resistance present in the treated dogs, and this took about 3 months to return back to baseline, and in some dogs it never did, so they wound up with permanent carriage of resistance, which means for the next infection, we may have fewer treatment options. So one of the keys of, of any antimicrobial stewardship programme, an antimicrobial stewardship really is, is the process by which we, preserve the efficacy of these drugs for the future.
One of the hallmarks of this is going to be that we need to use fewer drugs. Now it's difficult to say how much is too much, but this was some data that was done using the VET Compass system from the Royal Veterinary College and the SANET system based at the University of Liverpool. And what these do is, basically put up, almost like a virus on your practise management software and then they can use that to interrogate, you know, almost anything that's going on, within the practise.
And for the first time, this is when we can look at data from hundreds of thousands of animals, rather than a few tens or a few hundreds. And this data start showed that of the dogs and cats that were seen, something, somewhere between 20 and 30% of the consultations resulted in the use of at least one broad spectrum sorry, systemic antibiotic, and the majority of these were, were broad spectrum agents. HPCIA stands for highest priority critically Important antimicrobials.
So these are are the drugs that the World Health organisation has determined are critically important for human health. And there was quite a significant use of these in the dogs and cats in the study. And this would almost all be accounted for by cefovacin, which is a 3rd generation, cephalosporin, that 30% there again would, would be almost certainly cefovain.
So in other words, Something in the order of a third of the cats that received an antibiotic received aerobicin which has a a two week duration and the data from the SASnet was was very similar. And there's a couple of things that I would, I would point out here. Again, a very high proportion of, of cats receiving shoves in there.
And then in this group here, so this is puritus. So puritus is my day job as a dermatologist. This is what I do day in and day out.
And my antibiotic use is, is nothing like that. So it's hard to say how much is too much, but I think this data was indicating that, that we are using, too many, courses of broad spectrum antibiotics in dogs and cats. Now, more recently, the picture has improved.
and in particular, there has been a reduction in the use of these drugs as first-line treatment options for respiratory disease and gastrointestinal, presentations. So this was a study that I did with Kay Curry and Paul Flowers who are based at Glasgow Caledonian University, and they've done a lot of work with the National Health Service looking at what drives us to use antimicrobials and how we can then inform and and address intervention measures both for the general public, in, in our, terms, the animal owner and the clinician to, to reduce the use and, and, a lot is, is down to our individual prescribing behaviours and how these interact with, with the practise and with the client. And again, this is a very complicated behavioural study, but this is some of the take home messages here.
So basically the better. The knowledge around antimicrobial resistance and this was true both for the clinician and for the owner was was less antibiotic used. And then this this is a really interesting area because when we questioned owners, oh sorry, when we questioned the vets, the vet said the owner asked me for antibiotics.
The owner wanted antibiotics. When we asked the owner. The owner said the vet gave me antibiotics, but because I trust the vet to make the the the best judgement, I assumed that that was appropriate and the animal had an infection so.
I can't remember what people say, but something like 90% of communication is, is, . Nonverbal. And so a lot of this client demands seem to be really perceived than real.
And then both parties agreed that better communication would would help things, but this could be constrained by short consult times and this led to this just in case use. And this is because nobody wants a treatment failure. So the owner consciously or subconsciously is expressing a desire for their animal to get treated.
They don't want to, the owners feel very responsible for their, for their pets. They want to make sure that they get the right therapy. And then once you start down that slippery slope of saying, what if it's an infection, just I'll give an antibiotic just in case and then you start thinking, what if it's a mixed infection or the gramme negative is present?
Well, maybe I should use a broad spectrum drug and so on. And then a really big thing we found was the practise culture. So apologies to anybody in the audience but.
Roughly speaking, if you're, in your 40s and older, you are generally much less good at antimicrobial stewardship than vets who are younger than that. So what we found is the younger vets, were, were very aware of the message around antimicrobial stewardship and resistance. But in practises where the policies were informed on what was done, what had been done over the last 20 years and continue to do so, they didn't feel that they wanted to rock the boat and so they adapted themselves to the practise culture and that was a barrier to change.
Now this was some survey data done by the Bella Moss Foundation and, and Anna Mateus at the Royal Veterinary College. And I actually followed this up with an informal survey in a, in a webinar a couple of years ago. And, and unfortunately, the results weren't that different.
So, the, the, the problem is that we have a high number of clinicians. Still prescribing its antimicrobials without a diagnosis on this sort of speculative or or or just in case you and really what we want to be doing is shifting these bars downwards and ensuring that that we work on confirming the diagnosis. So the key steps really in antimicrobial stewardship are to ensure wherever possible that we've made the the diagnosis of bacterial infection or at least we have a very high index of suspicion that there is one.
And then it's always worth taking a moment to ask yourself whether it needs antibiotics and I'll come back to that later. It is a very important question. And then if it does, we need to select the appropriate drug, give it at the appropriate dose for the, for the appropriate duration.
And then really, really importantly. The vast majority of the infections that we see in in most body systems involve commensal or opportunist bacteria. So if it comes back, it doesn't mean that your course of treatment has failed.
It means that there is an underlying disease that needs managing for long term cure and this is a severe. Eosinophilic granuloma and plaque in a in a rescue cat that had been given a shed load of of erfovisin and eventually presented with with an MRSA infection. And all we did was treated it with a topical antiseptic and then gave it some an aggressive steroid course until we got the sinophilic plaque under control and the MRSA which sounds counterintuitive, but the MRSA was there because of the synophilic plaque.
To make the MRSA go away, we have to get rid of the earsinophilic plaque. Now there's a lot of talk about, about using cultures and, and we're going to spend a fair bit of time this evening about how to use that and how to interpret cultures, but really a very important thing sorry, very important area that's overlooked is, is just simply looking at the clinical signs and the cytology because this can help you diagnose the infection. Identify the likely bacteria, and what and and once you've done that with the knowledge of what are the bacteria most common at that site and that would fit the morphology you've seen on cytology, knowing your local practise figures, you can then work out what their likely susceptibility is.
Now, to a certain extent that is gambling, which is why the roulette wheel is here. But by understanding the type of bacteria you have you can shift the odds in your favour. And this means that you can use bacteria bacterial culture and sensitivity where it's appropriate and not have to rely rely on this in every case and we'll go through this.
Through this presentation. So it is worth revising the clinical presentation of infections. Now this is and I'm not going to go into this tonight because we don't have the time, but this is the, the accepted.
Classification for, skin infections now. And again, if you want to read, read that up in more detail and look at the pictures, there are, there are some very good resources available here. And by understanding those clinical signs, and this is the same for other body systems or maybe a little slightly harder for in that you can't see them but easier for the skin.
But by understanding that. Already you can have quite a good clinical impression that there is a high likelihood of infection there. And then the other thing you can do with the with the clinical signs is, is look to see how complex and severe that infection is because that's going to influence the treatment choices as we'll see later on.
Now the usefulness of cytology is that it shows. The biological response to the bacteria and this can help you differentiate between a commensal contamination or a mild overgrowth and confirm the infection. And again, it's something to use alongside the culture.
Rather than in instead of because it still gives you useful information. So firstly, it shows you that the body is responding to the bacteria. You have a neutrophil response.
The bacteria are being ingested by the neutrophils. You can then see which bacteria are being ingested by the neutrophils, which will tell you which ones are most important. And that can be very useful in mixed infections.
Or where you get a situation where the culture comes back with 3 or 4234 different organisms with different susceptibility patterns, but when you look at your cytology, you can say, well, actually the only one I saw with these with these cock eyes, so those are two other rods are probably not relevant. They, they're just contaminants. Also, cultures sometimes fail to pick up an organism.
So if you, if, if your cytology comes back and sorry culture comes back only showing Staphylococci, for example, but you also saw rods on your cytology, then you know something's not quite right. And it can be very useful to actually give the lab the cytology findings when you send the the cultures away which can help the microbiologist interpret the culture for you. Again, I'm not going to go through how to collect cytology.
There are lots and lots of resources for that. But the main thing is really both the culture and cytology is to make sure that the samples are representative because you really want to get this right first time. So it's about understanding the clinical signs.
And knowing where to collect your sample from. So from the epidermal choleet here, which would be this area here, we know that the bacteria are underneath the leading edge of that scale with the pustule, it's fairly obvious that the representative bacteria or the causative bacteria are here. But when we look at the deeper lesions, so the sinus tracts here.
And the ronchiosis here, then the back, the representative bacteria are either in the ruptured material in the dermis or in the subcutis or or deeper structures and anything on the surface here might be just a contaminant. So it's about understanding it to make sure that you go to where the primary disease is. And this is just to show you what a staph infection looks like.
Again, all of the bacteria that's staying up with the diffqui type stains stain dark blue. So, whether they're gramme positive or gramme negative, you can't you you have to infer that, but we can't tell that. And Staphylococci typically form pairs and then groups of 4 or tetrads because they split into two planes and then they'll form irregular clumps of bacteria.
So this pattern here is very, very typical of Staphylococci. Other cocci tend to just split in one plane, which is why they tend to form chains like streptococci. And if you see intracellular bacteria here, again, you have made that biological connection with the infection, whereas just a few bacteria in the background may just be contaminants.
These are a couple of rod infections. Now again, all of the bacteria that's staying with diff quick type stains stay in dark blue, so we're inferring that these are gramme negative based on the most likely organisms. This is a postoperative wound infection, and this turned out to be an E.
Coli. But we could have predicted that, and then this was a supparative ear infection. Again, we're showing biological response with the ingested bacteria here and again, that turned out to be pseudomonas, which would be the most likely organism in that situation.
This is a slightly different . A situation of called bacterial overgrowth syndrome. And what we have here is a very large number of bacteria, but no or only a few inflammatory cells.
So technically this is an overgrowth rather than an infection, but that doesn't necessarily say that it's non-pathogenic. Again, most of the bacteria here are Staphylococci, see these pairs and groups of four of these large cocci, but they are also. More filamentous bacteria here, there are some small cocci groups of cocci chains, there are some rods as well.
And these mixed patterns of bacterial overgrowth are particularly common. With biofilm formation and biofilm formation can be seen almost anywhere so we see this in body folds, lip folds, dental disease because this is what causes plaque and tartar. We can see this in urinary tract infections with urus, with catheters, orthopaedic implants, wound infections, and so on.
Now at this stage, we should have a very good clinical idea that there is likely to be an infection. And then we should also, have confirmed the, the infection, by the, the cytology and give us a good idea of what the organisms are likely to be. And therefore if we can tick all these boxes here.
Then we don't necessarily need to do a culture because we've got a fair idea that our empirical choice of antibiotic, or first line choice of antibiotics should be effective. Now this is appropriate for topical therapy and this is because cultures are very poorly predictive of the response to topical therapy and we'll look at that later. And then obviously if you have a life threatening infection, you can't wait to get your culture results back because you have to start treatment immediately.
So in this case, what you have to do is confirm the infection by clinical signs and cytology. And then make the best guess that you can. It to choose the most appropriate drug and in this case, we would probably err on the side of moving towards.
Broad spectrum drugs or maybe even 2 or 3rd line drugs because obviously in a life threatening infection, we don't want to, we want to minimise the chance of a treatment failure. Now this is where bacterial unconscious and sensitivity is recommended. Now I've already mentioned life threatening infections.
So we will have started treatment, but we now want our culture to confirm that the appropriate antibiotics that we can interpret later. And then anything that's a bit strange, so complex infections that are going to need prolonged treatment of antibiotic or have mixed bacteria on cytology, anything where the clinical signs and cytology don't fit, so it looks like an infection, but you can't confirm this on cytology or vice versa. And then I've put rods here because their their identity is much harder to infer from cytology.
So in other words, Klebsella, E. Coli, Proteus, Pseudomonas will all look very similar but have very different susceptibility patterns. So it's less easy to to predict their susceptibility compared to cockey.
And then anything where we have a treatment failure, because there are lots of reasons why. treatments don't work, but, 11 is the owner never gave them, but, we have to at this point consider, antibiotic resistance. And at the moment these are, are the factors that have a strong.
Link to antimicrobial resistance. Now again, the biggest one is multiple antibiotic courses, but then anything that's healthcare associated, so anything that's postoperative or healthcare acquired are all risk factors as well. So if we see any of those, then we should be straight on to taking a culture and these are a couple of MRSP cases.
This is around . External fixator, and this is a non-healing wound poster mammary tumour removal. I mentioned earlier about when to start treatment immediately.
And this is something that is, is going ahead in human medicine. It's also being used a lot in Scandinavia, where generally their approach to antimicrobial stewardship is, is well ahead of the rest of us and then coincidentally, they also have much lower rates of of resistance. And the the choice you have to make really is when to start treatment.
Now this dog here has a very superficial bacterial folliculitis there. One hates to be absolutist, but that's never going to kill that dog. Again, a delay if we if we have to take a culture.
We can treat the itch, symptomatically. We can use topical antiseptics, but we can wait for a few days to get that results back. This cat, .
Had severe abscessation and sinus tract formation with an actinomyces infection. Now this had been going on for more than 9 months by the time the cat was referred in. This is a very slowly progressive infection again, although it looks very severe, a delay of 2 or 3 days waiting for the results is not going to affect the clinical outcomes so we can treat symptomatically, whereas this dog had a Staphylococcal cellulitis.
And was going into toxic shock syndrome, following orthopaedic surgery. If we don't start therapy, that dog is going to be dead by the morning. So it, it's about looking, making the best choices that we can in that situation, but, whilst waiting for our cultures to come back, but for these two, time is on our side.
And if we have started treatment, . Whilst we're waiting for our culture, if that's justified, what we need to do is then when we get our culture results back, look to see how those work in terms of our, our treatment choices. Now, obviously, if, if we've underplayed it, so the infection is, is not susceptible or not completely susceptible to the antibiotic that we've chosen, then we need to escalate treatment up to a higher tier or a more broad spectrum drug.
And that's fairly obvious. Most people are going to get that, and the bit that isn't done. There's the de-escalation here and this is to be always thinking when you get the results back, what is the most low tier narrow spectrum drug that I can use?
Is there something I can de-escalate down to? And this is data from cases in our own hospital showing that whilst about 2/3 of cases here were appropriately de-escalated following culture results, about 1/3 won't, weren't sorry. And there are a number of reasons for that.
One was people tended to look at the results to justify their original choice and not look at the, the whole antibiogram. Another one was this common, belief that once you start a course of antibiotics, you have to complete it. And you don't.
What we're saying there is that it's the course of treatment that should be completed. And that doesn't matter if that's made up of two different types of antibiotics. So for example, 2 days of a fluoroquinolone followed by, let's say 12 days of clindamycin to clear an infection is better.
So de-escalating to the clindamycin is better than doing the whole 14 days on the fluoroquinolone. And the third reason we came across whereas people who given out the full 2 weeks of antibiotic before they got the culture results back and therefore didn't want to change and involve the owner with extra expense. But de-escalation is a very, very important tool in helping to minimise the use of inappropriately high tier and broad spectrum drugs.
I'm going to spend a bit of time going through culture results because it is is a bit of a complicated and controversial area. And there are two ways that these are reported. One is by using the Kirby Bauer discs, and what these do is measure the zone of inhibition around the antibiotic impregnated paper disc and then that zone of inhibition.
Is compared to, to, agreed break points. And then that is used to determine whether or not the and the infection is susceptible or resistant to that antimicrobial. And MIC methods actually calculate the minimum inhibitory concentration, which is the lowest concentration of antibiotic that inhibits the bacteria growth in vitro, and again that MIC is then compared to the break points to determine whether the infection is susceptible or resistant.
Now break points, . Are based on what happens to the drug when it gets into the body. Now these are usually based on oral administration, which is why sometimes intravenous antibiotics can be more effective because you don't get the the losses through the uptake and the bioavailability here.
But essentially, it doesn't quite work like this, but it's an easy way to imagine it. The break point is the highest level. Of antibiotic you're going to get in the target tissue following standard dosing.
Now, if the break point is higher than the minimum inhibitory concentration, so in other words, the tissue level is greater than the, than the lowest concentration of antibiotic needed to inhibit the bacteria, then that should be effective and the infection should respond to treatment. But if that break point, so if those tissue levels are actually below the MIC, then what you have is inadequate or subtherapeutic levels of antibiotic at the tissue level and therefore it is not likely that the infection will respond to treatment and that's how these break points are used to determine susceptibility and and resistance. Now what you will see is this intermediate category.
And the intermediate category basically is used. To give the lab a bit of wriggle room where there is insufficient data to produce a breakpoint or there are variables in the way the bacteria behave in vitro or it is more variable where the, how the antibiotic behaves in an individual because remember these breakpoints are just averages of the tissue distribution. Or where the breakpoint has been extrapolated from one species to another because again the tissue distribution can be species specific.
Now in practical terms, if you see an intermediate, it generally means that the tissue levels are subtherapeutic, but what you do know is that it's going to be very, the break point is going to be very close to the MIC. So if there's some way that you can increase those tissue levels. Because the drug concentrates in the target tissue, for example, penicillins in the urinary tract, or you can double or triple that dose safely, then you can still get a therapeutic response.
Now the Kirby Bauer disc data just tells you susceptible intermediate resistance resistance, sorry, and it doesn't tell you how susceptible or how resistant the that that infection is. And this is what the MIC data can give you, and this can give you some extra information about appropriate drugs and appropriate doses, but you do need to know how to interpret the antibiogram. And I'm going to go through a couple of examples.
So this is the sort of data that you get from IDEX currently. Ignore the antibiotics and the bacteria. It's just here for, for an example.
So what we have is the isolate, the drugs, the result, and then the figures which I'll come to in a second. Now the result is the headline resistant sensitive. Now, if you had Kirby Bauer this data, that's all you will see.
And the MIC data here gives us much extra information. But you can't compare MICs between drugs because they're unique to the drug and it's pharmacokinetics. So for example, you can't say the MIC of Tobramycin here is 4 and therefore that's much lower than carbaicillin at 256 and therefore that's, that's a better drug.
The value is where the MIC fits in terms of the break point. Now the letters here refer to the reference range, the concentration of antibiotic, the bacteria we're cultured with, and the extremes here are represented by the two numbers, and these are always micrograms per mL. So for any refluxes in here you have so they're always doubling dilution, so 2 mcg per mL.
1 mcg per mL 0.5, 0.25 for Marbafloxacin it's 4 to 1.5 for potentiator sulfonamide 320, 160, 80, 40, 2010, and so on.
Now ignore the capital for a second, and we'll use potentiated sulfonamide here as an example, but the switch from S to R is the break point. So in other words, and I said it doesn't quite work like this, but it's a useful way to to visualise it. What, what has been agreed is that, if the MI, sorry, the, the, maximum tissue level that you can, you can achieve in the body is going to be somewhere between 40 and 80 mcg per mL.
This is 1020, 40, 80, 160, 3, 20. So in other words, if the MIC is a minimum in concentration of antibiotic required to inhibit the bacteria. Is 80 or above, then that is higher than the tissue level and you, it shouldn't respond, so that will be called out as resistance.
But if it's 40 or below, then that will be exceeded by the tissue concentration and therefore you should see a a response to treatment. So the change from S to R here is the break point. There are a few here with the intermediate category we talked about earlier.
Now the capital refers to the value here and tells you where the break point, where the MIC is in relation to the break point. Now, unfortunately because these are narrow ranges, many of these are are off the scale. So in other words, the bacteria grew at every concentration they were tested.
So I don't know if the MIC here is going this way. 4 mcg per mL or 400 mcg per mL. I can't really interpret that.
But we do have 4 antibiotics that are read out as sensitive. Now if we look at icacillin Tobramycin. The MIC is one dilution for break points.
So in other words, the tissue levels are sufficient to treat the infection, but only just. And so if there is any problem with dosing. administration of the drug, any variation in bioavailability on pharmacokinetics, any problems with, with tissue penetration, and what you could find is that the actual tissue concentration is lower than is predicted by the in vitro test and you could see a treatment failure.
So if you do see your MIC here right up against break point, then what you want to do is increase the dose and or the frequency of the drug to max out your tissue levels and minimise the risk of a treatment breakdown treatment failure, sorry. Now if we had a choice between drugs and we compare pipericillin with the icacillin and the Tobramycin here. The MIC is at least 4 dilutions below break point.
So in other words, the ratio between the breakpoint and the MIC is much larger. And that means if we do get some loss, so if our tissue level is not quite as high as it as is predicted, that will have less impact and it should still be therapeutic. So it's much less vulnerable to to a treatment failure and that's the added advantage that MIC can give you by looking at where the ratio between the MIC and the break point.
It can tell you which is the most appropriate drug. Or indicate that you need to be thinking about increasing the dose or frequency. Now this is something that's becoming more common these automated fine tech 2 machines basically give you the same sort of information, so basically where it came from this is an esophageal tube wound infection, what the organism is, this one's an extended spectrum beta lactomase positive isolate and that that is one of the, one of the bugs that we're worried about because it confers quite a lot of resistance.
And then it'll tell you which ones are sensitive and it'll tell you the MIC. Now one of the disadvantages of the Vitech2 is it doesn't actually tell you what the MI the tested MIC range is. So what you have to do is get that information from the microbiology lab.
So this is another one here, so again another ESPL resistant E. Coli. What I've done is put together the sensitive the the the antibiotics to which it's sensitive to here with the MICs.
And then what I've done is gone to a table that we have at work and looked at what the clinical breakpoint is and then calculated the ratio between the break point and the MIC and basically the higher that ratio, the better. But if that ratio is down to 1, then it means that we're there again, that's we're very close to the the MIC is very close to breakpoint. And therefore we need to be considering altering dose or frequency to minimise the risk of a treatment failure.
But with the Vitech 2, you need to work with your laboratory to make sure that you have an up to-date table of the clinical breakpoints that are being used so that where necessary you can then calculate the MIC to breakpoint ratio. Now this table I'm not gonna go through it in detail and I've asked the webinar vet to see if this can get emailed out to everybody. But basically what this does is tells you, it gives you some added information to be able to infer predicted susceptibility or resistance based on the drugs that you have because they can't all be tested.
So instead of having to go for further testing, it can give you some immediate information on that. Now I said earlier that we don't tend to use cultures when we're considering topical therapy, and this is because the break points for susceptibility and resistance are all based on microgram per mil because they all are based on the premise you're treating systemically and the predictive value of these in terms of the clinical response to topical therapy is, is very poor because with topical or local therapy, remember you can get. Topical therapy, skin, ears, eyes, body folds and so on, but you can also flush bladders, flush joints.
Instil antibiotics into tooth roots and so on. You're limited really only by your imagination here. But, but you're achieving milligrammes per mL concentrations, so some hundreds to some thousands for higher levels which can overcome apparent resistance that only use culture to identify the organism to tell you which antibiotics are likely to be effective, but don't get overly.
Hung up on the susceptibility resistance results. Now I said right at the beginning, even if you diagnose an infection, you ought to ask this question, does it require a treatment or does it require systemic treatment because then a lot of time . Situations, the answer is no.
And in particular, remember I said right at the beginning, if you have recurrent commensal infections, you need to be managing the underlying disease. Now when I was a student and a young vet, I was taught never to use steroids or drugs like these, in the face of a skin infection. And now we're getting smarter.
I'm thinking, well, why is that infection there? Why is that staphylococcal infection there and if it is there because we have. Unmanaged atopic dermatitis, we need to get that inflammation and itching under control as part of our treatment.
But a lot of times using these alongside topical products is, is effective. And several studies have shown that chlorhexidine is highly effective, very broad spectrum, will overcome resistance and can be as effective as systemic treatment. And this is the topical antiseptic that has the best evidence to support its use.
There, there, there are others and this really now is the first line treatment for a surface or superficial skin infection, before we will start looking at systemic drugs. And certainly the shampoos and sprays, residual activity has been demonstrated on skin and hairs. Which means that twice weekly bathing is.
Is entirely appropriate and in fact the new DuxXO S3 protocol. Involves 3 week cycles of 1 thorough bath and one advantage of that is that could be done in the practise or at a grooming parlour for example. Followed by an application of a non-rinsing mousse, every 2 to 3 days and what that can do is improve the compliance, particularly where you have situations where thorough bathing for whatever reason is going to be difficult.
And there are some surprises and and one thing that you ought to be looking at when considering topical antiseptics is the evidence for their efficacy. And one of the problems we have is that these can be classed as medical devices or or non-medicinal products and therefore if they're not prescription products, they you don't need to demonstrate efficacy. So you can claim all sorts as long as you stay just this side of a medicinal claim.
And this is a study that we've recently published looking at antimicrobial wipes. And what we found is that whilst in vitro, at least the chlorhexidine products seemed to be effective against both susceptible staid intermediates and MRSP and E. Coli against more the more resistant E.
Coli, it was less effective and there was no efficacy against pseudomonas at all. So again, this is not a product we would use where we suspect Pseudomonas. And in fact, when we looked at .
Acetic acid, boric acid wipe product, we showed no antibacterial efficacy at all. And one of the things I recently learned is that the word antimicrobial implies a medicinal claim. But the word antibacterial anti-fungal doesn't, and I'm still sat here thinking they're the same, but in regulatory terms they're not.
So again, if somebody's trying to sell you a new product, then, what's the word I'm looking for you know plenty of time to become old and cynical like me, but at least be sceptical and ask for the at least the in vitro evidence to show that this is effective. This is hypochlorous acid. Hypochlorous acid gives a very rapid and very broad spectrum kill even against quite resistant organisms here.
But there's no residual activity on the skin, so it's like alcohol. It has its effect and and and then it's gone. One advantage of it is.
That it's very, very tissue safe. So this is, this is less good where if you want any residual or penetrating activity, but if you need to flush wounds, eyes, ears, tooth roots, bladders, things like that, we're using a lot of this now because of it's very, very, very, very tissue safe. The reason we use the Renaissance products here, is that to my knowledge, they're the only hypochlorous acid product in the UK.
That meets the EU, minimum standards for efficacy, safety and stability of biocides. I say there are lots of others. There, there is an increasing amount of evidence for, for these other products.
It is likely that they will become more mainstream, give us lots more options for non-antibiotic topical treatments. But again, as I say, do have some degree of scepticism, and be aware that if it's not a licenced product, those claims may not have supportive data. A topical antibiotics would be the, the next, .
Treatment choice and topical antibiotics are useful because they attain very high local tissue concentrations. So as we said, milligramme per mL concentrations, which can be very effective and help overcome resistance. But at the same time, the, the, the total body dose is, is much, much lower.
So the collateral damage that we're having in terms of selecting for resistance amongst the rest of the microbiome. Remember those graphs I showed you right at the beginning in terms of mucosal staphylococci, gut E. Coli, and so on, is much, much less.
This is sort of combination we would use if we saw gram-negative bacteria or mixed infections. And the fucidic acid here is highly effective against Staphylococca including MRSP. And the reason I've put muricin as a question mark there is that's largely used in humans for MRSA, so it's perhaps one that we shouldn't be using in animals and reserving it for human use.
Now if we do decide that systemic treatment is, is justified, then. We have to appreciate that we're not just treating the infection, we're treating all of the bacteria through the body, and this includes all the good bacteria as well. And remember that the estimates vary, but for every human cell in our body or animal cell in our patient's body, there is between 3 and 10 bacteria, and most of these bacteria are essential for health and well-being and and and tolerance and and so on.
And we want to minimise the impact on the microbiome by treating specifically, as much as we can. And one way that's been looked at this is to, is to tear antibiotics into 1st, 2nd and 3rd line and then look at their spectrum of activity. And the first line antibiotics really are those that we should be using wherever we have a choice.
And what's really important to remember is that if these are appropriate for an infection, they are just as potent as what we regard as. Second or third line drugs, we should never be talking about weak, strong, potent, less potent antibiotics. They're either appropriate or they're not.
And certainly when it comes to the sort of gambling empirical style treatment, we should really only be using first line drugs. Anything beyond this, we should be justifying with culture. And there would be some examples of of drugs which would be considered first line drugs.
And again, these are not going to be appropriate for all infections in all tissue in all species, but there are usually options in there. And then I've put erfovis in here in a separate box because really it, it could be considered as a first line drug if, if there was no other way, . To get the antibiotic into the organism.
So if that long acting injecting is genuinely the only way and, and this means talking to the owner to do that, then that's fine. But it shouldn't be regarded as a default, not even for cats. Now second line drugs, which would be the 3rd generation cephalosporins and the fluoroquinolones as far as we're concerned really.
Are not necessarily ones that are going to cause more resistance, but where resistance is going to have greater impacts on human and veterinary healthcare, and therefore we must justify their use, using culture results. And the 3rd line drugs are either these that are very important for human and veterinary healthcare, we must preserve their efficacy for the future. And or where they're not, they're not licenced for use in animals.
I remember I said, remember I said that break points, which is what determines susceptibility and resistance. Are, can be species are certainly species specific and they can also be tissue specific. So in other words, if we're extrapolate, if we don't have breakpoints for animals, we're extrapolating these from humans and they may not be appropriate, we may be using these drugs inappropriately so we have to justify their use on culture, showing that first or second tier drugs are not appropriate.
And that we've considered the use of topical therapy before we go down there and these will be some examples there. Now remember I talked about highest priority, critically important drugs. So these are the ones that are reserved for the the the most seriously ill humans.
And really these should not be used in animals at all. These would be things like vancomycin, and assolid techoplain, carbapenems and so on. Now as a junior doctor, you couldn't use those drugs.
It would have to get signed off by a senior consultant. And that there is no justification for using these in animals at all. They should be reserved for the, for the, for human use only.
And in fact, in certain countries, Netherlands and Scandinavia would be examples, that would be a criminal offence to do that. And again, not surprisingly, the, they, those countries have the lowest levels of antimicrobial resistance. Now the, as I said, we always want to be aiming for the most narrow spectrum drug we can, so we're targeting targeting it towards the the organisms as narrow as narrowly as possible and avoiding collateral damage to the rest of er of the microbiome.
And again, this table, it, it comes from the, the gramme book and it's I'll talk to you later about, but it's a useful, set of guidelines that were published in 2016, by Siva of conflict of interest warning as I was one of the authors for this. And it's a very, very useful, table just to have a quick look to give you an idea based on your cytology and likely organisms, what would be effective and, and how you can edge things down to, as narrow spectrum as possible. Now I talked, when we talked about break points, I talked about .
Thinking about how to change doses and I talked about changing the dose and all the frequency. And this is because it's worth thinking about the type of drug that you have and it, it, it's pharmacokinetics. So concentration dependent drugs are the classic examples here would be fluoroquinolones and aminoglycosides.
The efficacy is the ratio between the MIC green line here. This is antibiotic concentration up there, and the maximum concentration. So these drugs really we only need to give once a day, but what we want to do is maximise that ratio.
So if we, if we, if our tissue levels are edging close to MIC what we want to do is increasing the dose to maximise that out. Whereas the time dependent drugs, things like penicillins and cephalosporins, for example, their efficacy is the time above MIC, not the level above MIC, only insofar as the higher the dose, the longer it will take to drop down again. And we want to be maximising that and technically it needs to be for at least 70% of the dosing interval.
So if we need to up our game on therapy with these drugs, that's why not only increasing the dose but increasing the frequency can be important and actually telling an owner every 12 hours is better than twice a day to make sure that we're very precise about what we mean and where we might want to increase the treatment interval to say every 8 hours. And then drugs that have a mixed effect. It's the area under the curve which starts to get mathematically complicated.
But these would be things like lincosamides, and remethane sulfonamide, sorry, lincosamides and tetracyclines, and this is where we can have a little bit of flexibility around dose and dosing interval depending on the, on the case that we're seeing and the infection that we're seeing. I also said that one of the limits to treatment is drug penetration, and this can result in lower the lower than expected. Concentrations of antibiotic at the site of infection.
And antibiotics that are water soluble, so again, penicillins and cephalosporins really only penetrate to the extracellular fluid compartment, which for most simple infections is OK. But if you have complicated infections with biofilm plus debris, . Poor vascular supply, poor tissue perfusion, you can wind up with lower tissue levels than expected and treatment failures.
So if you think that's a problem, you may need to increase the dose or consider the use of a drug with a with good tissue penetration, for example, doxycycline or fluoroquinolone or clindamycin to, to avoid that and get a . Maintain your tissue levels and there are some examples of drugs and the tissue penetration. So the drugs with very good tissue penetration here are the ones that are going to cross blood tissue barriers and get into sites of chronic inflammation, poor tissue perfusion, and so on.
And biofilms I've mentioned several times, and these are. Becoming increasingly common, and biofilms occur everywhere. So if you're not sure what a biofilm looks like when we're done this evening, go to your showerhead or your sink and just unscrew the, the showerhead or the sink trap and have a look at that slime underneath it and that's a biofilm.
Bacteria use biofilms to stick to surfaces. And they will do that on inorganic surfaces, so pipeworks, sinks, drains and so on, but they'll also do this on the skin, eyes, teeth, the urinary tract, urlis, sutures, orthopaedic implants, and so on. And this protects the bacteria, against the antibiotic because it physically impedes penetration of the antibiotic.
And there's a, this is an example again of a a non-healing MRSA infected wound that was associated with the biofilm and this veil like wispy material in the background here is the biofilm. You can see the neutrophils and the bacteria again, mainly cocci and staphylococci here bound up in in that matrix. And as soon as we see that or suspect that, we need to be thinking about measures to to get on top of it to improve the therapy.
This is still slightly controversial, but in human medicine, the National Institute of Clinical Excellence, NICE, has produced a paper a couple of years ago now called 5 Days Is Enough. And basically they've reviewed the evidence and decided that 5 days treatment is adequate for the vast majority of simple, uncomplicated first time infections, no matter what the tissue. And still in veterinary medicine, we're treating for a lot longer than that, although the recommended guidelines are now dropping.
So if you look at the most recent UTI guidelines, that's a week for a simple first line infection, and we're looking at the same in skin. Really what we want to be doing is treating the clinical cure, which is resolution of lesions in normal cytology. Now the culture.
You have to interpret carefully, because if the bacteria shouldn't be there, then the culture should be negative. But if you have a skin infection here, you will still culture Staphylococci from that at the end of treatment because they're a commensal. So a positive culture doesn't necessarily mean a treatment failure.
You have to interpret that in terms of the lesions and the cytology. Now again, this is the survey done by Anna Mateus and the Benamos Foundation, . And this is getting a little bit better now, which is, which is good.
So, so when we repeated this, we, we did see the yes creeping above 50% there. And there's really very little excuse for not using antimicrobial stewardship guidelines in practise because there are loads of different ones available for whatever type of practise you do or however you, you, you want the the the format. And the BSAVA protect ones here are particularly easy to use.
There are lots of posters that they produce, there's a wall chart where you fill in your top three antibiotics for each, . The practise policy for for each tissue, for example, and this really helps the practise stick together. So it means if you ever are in that situation where you have a difficult client demanding antibiotics, they can, you, you have the guidelines to back you up and and support your decision making.
BSAVA also produce. A non-prescription pad where you can give that to the owner and it basically says this is why you're not getting antibiotics and that's very, very useful and helps overcome some of the communication problems we see with with short consult times. I mentioned the gramme book, This was published by Siva.
It's now, it is available as as a book form. It's also available online. I guess if you only wanted one practise resource, this is a fantastic one to have because it basically gives you all the information that you need to know in terms of very, very quick, reference guides to treatment choices, all the backup information that you need in terms of.
Understanding antibiograms, how to take samples, how to do cytology, and so on. And then some more in-depth topics around resistance, infection control, prophylactic use in in surgery and so on. So it's a fantastic practise resource.
This is something to think about if you've not yet got involved in it and this is, this is my SASnet AMR. Basically what SAnet does, as I said earlier, it sits as a little programme on your practise management software and then can act as an interface providing the data for you, for your, your, your in practise clinical audits. Now the AMR bit monitors antimicrobial use within, within the practise structure and what they can do is provide you with information.
Showing how much you've used patterns of use between different staff and different cases, but also allows you to compare your use of an antibiotic to similar practise so you can look at where you are in terms of median and so if you're if you're below medium, that's great, but it's not time to be complacent I guess. But if you're above median, it can be that early warning to say hang on. Let's have a look what's, you know, can we justify this or other measures that that we can take to improve our stewardship.
So I'd, strongly recommend that you, get involved in that if you haven't done so already. And then just to finish up, the, yeah, who knows, what's going to happen, technically this is not part of the European Union, but, . Anyway, I'll, you can go onto the website.
It's usually 3rd week in November. There's lots of stuff you can download. There's lots of activities you can do to encourage antimicrobial stewardship within the practise and within your clients.
Antibiotic action, I'm an antibiotic action champion. It's maybe a little bit more for specialists within the fields, but this is something everybody can do. It's a bit like antibiotics Anonymous.
You go on and you make a pledge, and the idea is that then that focuses your mind on trying to do employ stewardship better with within your practise. And anybody can do this, so this, it can be vets, nurses, receptionists, but also clients. So this is something you can advertise in the waiting room and again get your clients on board with antimicrobial.
Resistance and stewardship goes a long way to helping you make the right choices. So again, thank you very much for listening and I'm happy to take any questions. Tim, that was absolutely fascinating.
And your explanations of the, the MICs and, and, the breaking points and that was, was just insightful. It made it so easy to understand. So thank you for your time and thank you for your expertise in sharing it tonight.
You're welcome. We've got a couple of questions coming through. What is your opinion of the bioluminescence test for UTIs?
It's not something I'm hugely familiar with, the, the. There, there is a there is a number of these now that are being used for wound infections as well, . It tells you whether you have viable bacteria there.
It doesn't necessarily tell you that it's an infection. Or what the organisms are, so I think it's a useful tool, . But It it's not, it's something that wouldn't be standalone.
I would still do the sediment exam to then give you an idea of what the organisms are likely to be and then if necessary, send off for a for a culture. But I think it can be a very quick yes no. It can be very useful for that.
Certainly in wounds, it's very useful. For selecting areas for cytology, selecting areas for culture, but also saying how effectively have we cleaned that wound. Have we still got viable bacteria, present there.
I mean, UTI is a good example because, you know, even again, cytology, it's one of those things that has a steep learning curve, but it's a fairly quick one, and the more you do it, very rapidly, the more, well, first thing is get a decent microscope and look and get somebody to look after it, but once you've done that. You, you can become very confident very quickly with it. And, you know, at a very basic stage, everybody should be able to differentiate staphylococci from streptococci from rods.
And then once you get a bit more, you know, skilled and confident, you can then start to identify some of the different subtleties between. Caraniforms, coliforms and pasturella for for example, and knowing that can give you a very quick and immediate information about what, what are the likely organisms and then based on your own practise knowledge of resistant patterns and history of antibiotic use, for example, in the animal, you you can start empirical, you know, make, make the best guess you can, but you've shifted the odds in your favour of, of making an appropriate empirical choice. And then obviously you can modify that once your culture comes back, but that cytology also gives you really useful information.
To help you interpret the the the the culture results and so I think, I think this bioluminescent . Techniques have their place, but at the moment they're limited in the specific information they give you, but they can be a good yes no or tell you where the the bugs are in a wound, for example. Excellent.
an, an interesting perspective or question has come through from Arthur saying, you know, the, the difference between an owner battling to finish a course of antibiotics as opposed to, a single use of sevecin, as an injection. Yeah, and it certainly Right, well, I'll, I'll go back to when I was a student. This was when I was a 4th year student, and, and back in those days, we used to do our first opinion 4th year rotations at the PDSA centre in Bristol.
And we had a cat came in with a cat bit abscess and, and, . Power of of brand familiarity when when we were asked what would you treat this cat with we all piped up ingullocks and then we got a real row from the from the vet and he says I'm I'm ashamed to say I can't remember his name. He was very cool and he, he drove a sports car, but, he was ahead of his time because he said, no, if you do that, all you're going to do is select for resistance.
This cat is well, it's eating, it's not pyrexic. That's a nicely walled off abscess. We lance it, we keep it draining.
The cat gets some painkillers. And I, I do that with my own cat. I mean we've had 3 abscesses in the last about 18 months or so with, with, .
With our two cats and I haven't used a single antibiotic with them. So I think, I think that's the first thing you can always just think, does it need an anti a systemic antibiotic. Now, obviously if it's pyrexic unwell, there is some degree of cellulitis, then it probably does.
But . Again, it's back to this 5 days is enough. I mean, for some of those animals actually less than 5 days antibiotic will be, will be effective.
UTIs in people, sometimes 2 to 3 days antibiotics are effective. Rather than this default and we're going to use a 3rd generation broad spectrum cephalosporin that will be there for at least 2 weeks and possibly longer as it as it works its way out to the body. Now I'm not saying we absolutely shouldn't use that drug, but we should be able to justify it and it may be actually that.
You know, an owner, we don't need an owner to struggle for two weeks with, with, amoxicclaph or amoxicin or whatever we're going to use because actually 3 or 4 days of that and the and and the cat's done it's absolutely that abscess is, is healing up and we and we're good. But again, it's always worth thinking about, food disguising it, you know, and I always think if somebody could make a tablet that was basically dreamies, you'd have no problem giving them to cats. But, certainly thinking about, you know, what's the cat's favourite food?
Was it really like to eat as a treat, you know, R R2, if we need to give them a drug, just put it in yoghurt because they'll kill for that. Pate. using WikiLeaks, things like that.
Yeah. And I think, I think what you said there, hit the nail on the head. It's being able to justify what you do.
It's not a question of this is the right drug or the wrong drug or the whatever. What can you justify in that situation? And that's what I like about those protect posters.
Because when you sit around and discuss them, with the practise, it makes you talk about the justification for using it, not just out of habit, as you said, your sports car clinician was, was, berating you for. And he was absolutely right. And I think, I think also that discussion helps the practise come to a policy which means That, you know, we, we've, we've heard this from, from younger vets and I'm again, apologies to anybody in the audience who's over 40 and, and who's, really good on anti-micro with stewardship, but there was, a meeting I was, I was at in Solihullland in November.
And there, there was a practise group there who'd looked at antimicrobial use amongst their vets and basically if you're over 40 you were using more antibiotics than than the vets under 40. Yeah, but, but I think if you have a practise policy, it means that the, the, the, everybody's listened to, and it stops this, this, this feeling that the younger vets don't want to rock the boat. But at the same time, you know, it means that the older vets.
And again, apologies to the audience. Can listen to the younger colleagues and, and, and pick up what what what's changing, in treatment here. But it also means it gives people confidence because.
You know, some of this just in case use is what if I get it wrong? What if there's an infection, blah blah blah, you know, what if they go and see somebody else and they give an antibiotic and I'm gonna feel like an idiot. It stops that and the other thing, the other thing perhaps to point out is.
The fact that, you know, there is going to be the occasional case where you, you, you, you don't use an antibiotic, and then a week's time you're going to have to use an antibiotic and that's not a treatment failure. That is just moving on, because what you have to remember is the other 9 out of 10 cases that actually were fine and didn't need a systemic antibiotic. The overall gain in terms of stewardship is, is far greater, .
And I think if you explain that to an owner to say, well look, we're gonna do this because of blah, use the BSAVA nonprescription tablets, but if it's not working, we we we'll, you know, we now have this the the the drugs in the back pocket as it were. Yeah. Excellent, excellent.
Again, it comes down to being able to justify your decisions. Yeah, and again, 11 of the big things that came out of that meeting in in November was the, the labs were saying, you know, in the guideline, people the right guidelines were saying we're saying we're not telling you what to use because that has to be your clinical judgement based on on your patient. But what we're doing is setting up a framework to help you make the most appropriate treatment choices.
In terms of doing the best for your patient, but in terms of the bigger picture preserving these drugs for the future. And certainly the there was 11 lady who does sit on a on quite a high level European panel and she said that she would be very surprised if for We get any new drugs in the foreseeable future for treating animals. She said if, if a genuine new class of drug comes along, it will almost certainly be reserved legally for human use only.
Yeah. That's that's it, food for thought. And I think at that stage, we've run far enough over.
Tim, you have shared an amazing amount of knowledge, and I know you have stimulated thoughts. Hopefully, that people are going to go back and, and reassess their practise antibiotic stewardship and join the, the movement. Thank you for your time.
You're welcome. Thank you. And everybody that attended tonight, thank you so much again for attending.
My controller Dawn in the background, thank you for making this all happen and from me, it's good night.
